The enzymatic complex Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase (NOx) may be the principal source of reactive oxygen species (ROS). The NOX2 and NOX4 isoforms are tissue-dependent and are differentially expressed in slow-twitch fibers (type I fibers) and fast-twitch fibers (type II fibers) of skeletal muscle, making them different markers of ROS metabolism induced by physical exercise. The aim of this study was to investigate NOx signaling, as a non-adaptive and non-cumulative response, in the predominant fiber types of rat skeletal muscles 24 h after one strenuous treadmill exercise session. The levels of mRNA, reduced glycogen, thiol content, NOx, superoxide dismutase, catalase, glutathione peroxidase activity, and PPARGC1α and SLC2A4 gene expression were measured in the white gastrocnemius (WG) portion, the red gastrocnemius (RG) portion, and the soleus muscle (SOL). NOx activity showed higher values in the SOL muscle compared to the RG and WG portions. The same was true of the NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, glycogen content. Twenty-four hours after the strenuous exercise session, NOx expression increased in slow-twitch oxidative fibers. The acute strenuous exercise condition showed an attenuation of oxidative stress and an upregulation of antioxidant activity through PPARGC1α gene activity, antioxidant defense adaptations, and differential gene expression according to the predominant fiber type. The most prominent location of detoxification (indicated by NOX4 activation) in the slow-twitch oxidative SOL muscle was the mitochondria, while the fast-twitch oxidative RG portion showed a more cytosolic location. Glycolytic metabolism in the WG portion suggested possible NOX2/NOX4 non-regulation, indicating other possible ROS regulation pathways.

Physical exercise is characterized by an increase in physical and metabolic demand in face of physical stress. It is reported that a single exercise session induces physiological responses through redox signaling to increase cellular function and energy support in diverse organs. However, little is known about the effect of a single bout of exercise on the redox homeostasis and cytoprotective gene expression of white adipose tissue (WAT). Thus, we aimed at evaluating the effects of acute aerobic exercise on WAT redox homeostasis, mitochondrial metabolism, and cytoprotective genic response. Male Wistar rats were submitted to a single moderate‐high running session (treadmill) and were divided into five groups: control (CTRL, without exercise), and euthanized immediately (0 h), 30 min, 1 hour, or 2 hours after the end of the exercise session. NADPH oxidase activity was higher in 0 h and 30 min groups when compared to CTRL group. Extramitochondrial ROS production was higher in 0 h group in comparison to CTRL and 2 h groups. Mitochondrial respiration in phosphorylative state increased in 0 h group when compared to CTRL, 30 min, 1, and 2 h groups. On the other hand, mitochondrial ATP production was lower in 0 h in comparison to 30 min group, increasing in 1 and 2 h groups when compared to CTRL and 0 h groups. CAT activity was lower in all exercised groups when compared to CTRL. Regarding oxidative stress biomarkers, we observed a decrease in reduced thiol content in 0 h group compared to CTRL and 2 h groups, and higher levels of protein carbonylation in 0 and 30 min groups in comparison to the other groups. The levels returned to basal condition in 2 h group. Furthermore, aerobic exercise increased NRF2, GPX2, HMOX1, SOD1, and CAT mRNA levels. Taken together, our results suggest that one session of aerobic exercise can induce a transient prooxidative state in WAT, followed by an increase in antioxidant and cytoprotective gene expression.

Exercise has beneficial effects on energy balance and also improves metabolic health independently of weight loss. Adipose tissue function is a critical denominator of a healthy metabolism but the adaptation of adipocytes in response to exercise is insufficiently well understood. We have previously shown that one aerobic exercise session was associated with increased expression of antioxidant and cytoprotective genes in white adipose tissue (WAT). In the present study, we evaluate the chronic effects of physical exercise on WAT redox homeostasis and mitochondrial function. Adult male Wistar rats were separated into two groups: a control group that did not exercise and a group that performed running exercise sessions on a treadmill for 30 min, 5 days per week for 9 weeks. Reactive oxygen species (ROS) generation, antioxidant enzyme activities, mitochondrial function, markers of oxidative stress and inflammation, and proteins related to DNA damage response were analyzed. In WAT from the exercise group, we found higher mitochondrial respiration in states I, II, and III of Complex I and Complex II, followed by an increase in ATP production, and the ROS/ATP ratio when compared to tissues from control rats. Regarding redox homeostasis, NADPH oxidase activity, protein carbonylation, and lipid peroxidation levels were lower in WAT from the exercise group when compared to control tissues. Moreover, antioxidant enzymatic activity, reduced glutathione/oxidized glutathione ratio, and total nuclear factor erythroid-2, like-2 (NFE2L2/NRF2) protein levels were higher in the exercise group compared to control. Finally, we found that exercise reduced the phosphorylation levels of H2AX histone (γH2AX), a central protein that contributes to genome stability through the signaling of DNA damage. In conclusion, our results show that chronic exercise modulates redox homeostasis in WAT, improving antioxidant capacity, and mitochondrial function. This hormetic remodeling of adipocyte redox balance points to improved adipocyte health and seems to be directly associated with the beneficial effects of exercise.

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis, and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at three months old were divided into the following experimental groups: Sham-operated treated with vehicle (DMSO 10% + PBS – 1ml.kg-1); OVX (vehicle-treated) and OVX-Q (25 mg.kg-1) – via oral gavage, daily for five weeks. Q did not prevent weight gain, but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine TNF-α, compared to the OVX group. Q also improved antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) and decreased reactive oxygen species (ROS) production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

Obesity is usually linked to oxidative stress, which can lead to damage to biomolecules. The combination of aerobic and strength exercises seems to induce health benefits in obese individuals, but little is known about the effects of combined physical exercise on redox homeostasis and DNA damage in this population. Thus, the aim of the current study was to determine the effects of 16 weeks of combined physical exercise on biomarkers of oxidative stress and DNA damage in obese women. 17 obese women underwent 16 weeks of a combined physical training program, 3 times per week. Anthropometric and biochemical parameters, serum superoxide dismutase (SOD) and glutathione peroxidase activity, plasma 8‐isoprostane levels, and DNA and chromosomal damage were evaluated before and after physical training. Combined physical exercise training decreased body weight (83.2 ± 9.6 vs. 80.2 ± 9.6 kg), body mass index (33.8 ± 3.6 vs. 32.6 ± 3.7 kg·m^-2), body fat (40.2 ± 2.6 vs. 39.0 ± 3.2%), and waist circumference (99.3 ± 9.4 vs. 94.1 ± 8.8 cm), while the fat‐free mass was augmented (59.9 ± 2.9 vs. 60.7 ± 3.1 kg). Moreover, blood glucose reduced (113.5 ± 29.6 vs. 107.3 ± 28.9 mg/dL) along with high‐density lipoprotein (54.6 ± 18.1 vs. 59.0 ± 18.8 mg/dL), TSH (2.1 ± 1.1 vs. 2.6 ± 1.2 mIU/mL), and free T4 (0.9 ± 0.1 vs. 1.12 ± 0.2 ng/dL) increase after physical exercise training. Plasma 8‐isoprostane levels (17.24 ± 7.9 vs. 29.11 ± 17.44 pg/mL) and DNA damage (34.16 ± 7.1 vs. 45.96 ± 5.8% DNA in tail) were also higher after physical training. No changes were observed in chromosomal damage levels. These results suggest that 16 weeks of combined exercise training 3 times per week is effective in reducing body fat but also increases oxidative stress and DNA damage in obese women.